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D Williams

Publications and source records attributed to D Williams.

At least 253 records · Page 14Linked to original sources
PubMed1996

Mapping the human Y chromosome by fingerprinting cosmid clones.

We have used Y-specific cosmid clones in a random fingerprinting approach to build contigs on the human Y chromosome. Clones derived from two libraries have been analyzed. The construction of one library is described here, the second was the Y chromosome-specific library LLOYNCO3 "M" (Lawrence Livermore National Laboratory). To date, we have fingerprinted 4430 cosmids: 377 contigs have been constructed containing from 2 to 39 clones. Along with the singletons, we estimate that we have covered 72.5% of the euchomatic portion of the Y chromosome with fingerprinted clones. Sequence tagged sites are being used to anchor cosmids and contigs onto the YAC framework.

Base Sequence↗
PubMed1996

13-cis-Retinoic acid affect sheath-shaft interaction of equine hair follicles in vitro.

A major challenge to the study of hair follicle growth is an appropriate assay system. Because equine mane follicles are large and noncurved, enabling easy dissection; are readily accessible from a single defined source; and possess a long anagen growth phase, we initiated a study of them in culture. As in our previous studies of human and sheep follicles (Dev Biol 165:469, 1994), we found in this system that transection level dictates the pattern of follicle growth in vitro: follicles transected below the sebaceous gland show a type 1 growth pattern (the shaft grows out with an adherent sheath), while nontransected follicles show a type 2 growth pattern (a naked shaft grows out lacking a sheath). In the present study, we searched for compounds that might influence type 1 or type 2 patterns of growth. We found that 13-cis retinoic acid induced, in a concentration-dependent fashion, a type 1-like pattern of growth under conditions for which a type 2 pattern was expected. All-trans-retinoic acid, SR11237 (a synthetic retinoid X receptor-specific ligand), and meta-carboxy-TTNPB (and inactive synthetic retinoid) did not have these properties. We hypothesize that sheath growth¿processing is mediated by the follicle at the level of the sebaceous gland, or by the sebaceous gland itself, and that persistence of the follicle sheath about the outgrowing shaft in vitro (i) in the physical absence of the sebaceous portion of the follicle, or (ii) in the presence of 13-cis-retinoic acid, is due to the reduced expression of a factor that regulates important shaft sheath interactions.

Animals↗
PubMed1996

Ethanol-induced alterations in the posttranslational processing, but not secretion of luteinizing hormone-releasing hormone in vitro.

The effects of ethanol (EtOH) on the male hypothalamic pituitary reproductive axis are multiple and varied. Although direct gonadal toxicity has been reported, hypothalamic-pituitary perturbations have also been noted. The difficulty of sampling the hypothalamus has made direct investigation of EtOH-induced alterations on luteinizing hormone-releasing hormone (LHRH) fraught with interpretation problems. To circumvent this, we have conducted a series of experiments exploring the effect of 200 mg% EtOH in vitro on GT1-7 cells, a newly developed LHRH secreting neural cell line. Cell lines were treated with EtOH-containing or EtOH-free media for 2, 6, 24, or 48 hr. EtOH caused no significant change in LHRH secretion at any time point, although there was a trend to increased secretion after 2 hr EtOH exposure when compared with control. Significantly increased total (i.e., cellular plus secreted) pro-LHRH coupled with significantly reduced cellular LHRH after 6 hr only of EtOH exposure suggested that EtOH caused a transient decrease in processing from bioinactive pro-LHRH to bioactive LHRH. However, even at this time point, LHRH secretion from these EtOH-exposed cells was no different than from control cells. Steady-state LHRH mRNA levels were not changed by EtOH at any time point. These findings are concordant with previous in vitro data using hypothalamic tissue that has similarly demonstrated no effect of EtOH on LHRH secretion. Taken together with the in vivo demonstration that EtOH reduces hypothalamic-pituitary portal blood levels of LHRH, these data indicate that EtOH exerts its effect either at an extrahypothalamic locus and/or on non-LHRH-producing cells within the hypothalamus.

Animals↗
PubMed1996

Molecular mechanisms underlying he interaction of motuporin and microcystins with type-1 and type-2A protein phosphatases.

Heptapeptide microcystin and pentapeptide motuporin (nodularin-V) are equipotent inhibitors of type-1 and type-2A protein phosphatase catalytic subunits (PP-1c and PP-2Ac). Herein we describe elucidation of the molecular mechanisms involved in the interaction of these structurally similar hepatotoxins with PP-1c/PP-2Ac and identification of an important functional difference between their mode of interaction with these enzymes. Microcystin-LR, microcystin-LA, and microcystin-LL were found to interact with PP-2Ac and PP-1c by a two-step mechanism involving rapid binding and inactivation of the protein phosphatase (PPase) catalytic subunit, followed by a slower covalent interaction (within hours). Covalent adducts comprising PPase-toxin complexes were separated from free PPase by C-18 reverse-phase liquid chromatography, thus allowing the time course of covalent adduct formation to be quantitated. In contrast to microcystins, motuporin (nodularin-V) and nodularin-R were unable to form covalent complexes with either PP-1c or PP-2Ac even after 96 h incubation. Specific reduction of microcystin-LA to dihydromicrocystin-LA abolished the ability of the toxin to form a covalent adduct with PP-2Ac. Specific methyl esterification of the single Glu residue in microcystin-LR rendered this toxin inactive as a PPase inhibitor and abolished subsequent formation of a covalent adduct. Our data indicate that inactivation of PP-2Ac/PP-1c by microcystins precedes covalent modification of the PPases via a Michael addition reaction between a nucleophilic phosphatase residue and Mdha in the heptapeptide toxin. In contrast, following rapid inactivation of PP-2Ac/PP-1c by motuporin, the equivalent N-methyldehydrobutyrine residue in this toxin is unreactive and does not form a covalent bond with the PPases. These results are consistent with structural data for (i) the NMR solution structures of microcystin-LR and motuporin, which indicate a striking difference in the relative positions of their corresponding dehydroamino acids in the toxin peptide backbone, and (ii) X-ray crystallographic data on an inactive complex between PP-1c and microcystin-LR, which show a covalent bond between Cys-273 and the bound toxin.

Enzyme Inhibitors↗
PubMed1996

A shunt infection caused by Francisella tularensis.

We report the first case of a child with a shunt infection caused by Francisella tularensis, the causative agent of tularemia. This patient is also unique in that the disease was limited to the central nervous system.

Child, Preschool↗
PubMed1996

Staying calm under pressure: the secrets of bioceramics.

For very good reasons, ceramics as a class of material have limited uses in medical devices. They do, however, have some interesting, relevant, and unique properties. This article explains this paradox in terms of the structural characteristics of those materials.

Biomechanical Phenomena↗
PubMed1996

Complements of the season: the hazards of testing for complement activation.

As some of the subtleties of the new era of biological testing become appreciated, a few of the more recently introduced tests are starting to cause concern. The evaluation of the ability of a material to activate complement comes into this category. This article explains complement and its activation and attempts to rationalize the need for testing in this complex area.

Complement Activation↗
PubMed1996

"'Tis virtue not birth that makes us noble:" the role of noble metals in medical devices.

Gold, silver, platinum, and other noble metals are enigmatic with respect to their biological uses. On the one hand they are considered to be highly inert with excellent all-round biocompatibility and useful for electrodes and a variety of implanted and nonimplanted medical devices. On the other hand some noble-metal complexes are highly potent biologically. This column attempts to dispel some of the confusion.

Biocompatible Materials↗
PubMed1996

Paying and playing with plastic. The meaning of plastics, plasticity, and plastic surgery.

Plastics are not only the proverbial everyday commodity, but they also permeate almost every aspect of medical devices, from technology to clinical application. This article addresses some of the confusing features of plasticity as they relate to the materials called plastics, to the phenomena of material plasticity, and to the clinical and biological usage of the word.

Biocompatible Materials↗
PubMed1996

The paradox of being unique and ubiquitous: the nature of surfaces.

The surfaces of biomaterials are extremely important, but it is far from clear exactly which characteristics of material surfaces control medical device performance. This article discusses some of the classical features of surfaces that may be involved, including surface chemistry and energy.

Biocompatible Materials↗
PubMed1996

The beneficial effect of enhanced macrophage function on the healing of bowel anastomoses.

Inadequate healing and subsequent leakage of bowel anastomoses are serious postoperative complications in abdominal surgery. Previous studies have demonstrated the macrophage to be a key cell in the physiology of wound healing. The current study was undertaken to evaluate the effects of enhanced macrophage function on the healing of bowel anastomoses. Sprague-Dawley rats (250 gm) underwent laparotomy and jejunojejunostomy following IV treatment with glucan (100 mg per kg), a potent macrophage stimulant, or 5 per cent dextrose 24 hours before surgery and again on the day of surgery. Animals were killed and the anastomoses underwent wound tensiometry on Day 3 using a computer-assisted constant velocity tensiometer. The glucan treated animals had a significantly greater anastomotic breaking strength (88.5 gm +/- 10.7 versus 45.45 gm +/- 5.1) (P < 0.01). Formalin fixation increased the breaking strength of the untreated anastomosis but not of the treated anastomosis (92.9 gm +/- 11.77 versus 92.3 +/- 12.44). Analysis of macrophage supernatant for the growth factors epidermal growth factor (EGF), platelet derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) was accomplished by immunoblot assay. Results indicated no difference in the presence of EGF in the stimulated and unstimulated macrophage supernatants. PDGF and TGF-beta were decreased in the stimulated macrophage supernatants. We conclude that 1) Enhanced macrophage function had a beneficial effect on the early tensile strength of bowel anastomoses. 2) Effects of the activated macrophage on bowel anastomoses may not be related to secretion of conventional growth factors. 3) Immunopharmacologic agents that enhance macrophage function may be an important adjunct to surgical therapy requiring bowel anastomosis.

Analysis of Variance↗
PubMed1996

[editorial].

Explore the source record for details and available documents.

Biocompatible Materials↗
PubMed1995

Has improvement in PTCA intervention affected long-term prognosis? The NHLBI PTCA Registry experience.

BACKGROUND: The NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry followed 1345 consecutive patients with first PTCA between 1977 and 1981 (registry 1) and 2136 consecutive patients with PTCA between 1985 and 1986 (registry 2). Changes in patient selection and in immediate and 1-year outcome are presented. This report extends to 5 years the comparison of the effects of early and more recent management with PTCA. METHODS AND RESULTS: Sixteen participating centers entered consecutive patients who had angioplasty for the first time between 1977 and 1981 and between 1985 and 1986. Patients with recent myocardial infarction (MI) were excluded. Vessel disease was defined according to the Coronary Artery Surgery Study. Successful dilatation required > or = 20% reduction in luminal narrowing and < 50% lumen diameter stenosis after intervention. Routine annual follow-up was conducted by telephone interview. The product-limit method was used to estimate freedom from untoward events, Cox regression analysis to model relative risk and adjusted relative risk of events between the two registries, and logistic regression when the exact time of outcome (such as recurrence of symptoms) was not known. Long-term event rates were computed by vessel disease for all patients and for the cohort of patients with initially successful PTCA. After adjustment for extent of disease, diabetes, prior bypass surgery (CABG), hypertension, age, and sex, the 5-year risk of death was similar in the two registry cohorts. However, rates of MI, CABG, and a combined outcome measure of death, MI, and/or CABG were significantly lower in the registry 2 cohort both for all patients and for patients who were initially treated successfully. Use of repeated PTCA was higher, and freedom from symptoms without adverse events was significantly better in the latter cohort. CONCLUSIONS: Compared with registry 1, the management of the registry 2 cohort resulted in lower 5-year morbid event rates and reduced CABG operations. Mortality rates remained similar. When symptomatic status was considered in combination with events, a significantly better outcome was seen overall and in the initially successful cohort. In registry 2, repeated PTCA was used with much greater frequency early after the initial procedure.

Angioplasty, Balloon, Coronary↗